Pesticides are chemicals designed to cause biologic harm to plants, insects, and other pests. Widespread use in agriculture and in urban areas creates an opportunity for exposure to a large segment of the population.Epidemiologic investigations are undertaken to identify and clarify cancer risks from pesticide exposure. The Agricultural Health Study (AHS) is a major effort which is designed to evaluate the relationship between pesticides and other agricultural factors and the risk of cancer and other diseases. Enrollment in this study includes about 90,000 men and women from Iowa and North Carolina. From 1993-1997 detailed information was obtained by self-administered questionnaire and from 1998 through September 2003 computer assited telephone interview has up-dated the information collected at enrollment. Telephone interviews include questions on pesticides used and other agricultural exposures, lifestyle factors, medical and family history of disease, and diet. We are also collecting buccal cell samples as a source of genomic DNA on all members of the cohort. Analyses on cancer incidence and other chronic diseases is continuing and a number of manuscripts focusing on cancer incidence overall, prostate cancer, breast cancer and lung cancer are now published or are in press. Preliminary findings from the prostate cancer anlysis suggests a number of pesticides are associated with a prostate cancer risk. The risk of prostate cancer is particularly strong among those with a family history of prostate cancer. Analyses of non-Hodgkin's Lymphoma and a folow-up analysis of prostate cancer risk factors is planned for 2005. The Agricultural Health Study is also analyzing the cancer experience of pesticide applicators who have used chlorpyrifos, alachlor, atrazine, glyphosate, malathion, metoachlor, and a number of other pesticides of wide-spread use and toxicologic interest. Results from these analyses should be available from 2004-2005. A biomarker study [The Corn Farmer Study], nested within the AHS is assessing perturbations in the immune system of a group of Iowa corn farmers and a control group not exposed to corn farming, during a calendar year, some result are expected in 2005. In a case-control study nested with the Agricultural Health Study, retinal degeneration was significantly associated with exposure to fungicides and selected insecticides, further analyses is now being conducted on this finding. The risk of a high pesticide exposure event resulting in symptoms is more pronouned among farmers whose farms were in poor financial condition compared to those whose farms were not and among those with a higher risk acceptance than those with a lower risk acceptance. Several manuscripts with analyses of mechanical injury associated operating a farm have been prepared and submitted for publication. Several manuscripts with analysis of respiratory wheeze have been published indicating that diesel tractor use, work in poultry operations and exposure to several pesticides are risk factors for respiratory wheeze. These cross-sectional studies will be follow-up with additional longitudinal analyses in 2005.A study of Parkinson's disease nested within the Agricultural Health Study is now in the data collection phase of the study. Several other projects to evaluate the cancer risk from pesticide exposure are underway. Analysis of data from case-control studies of non-Hodgkin's lymphoma noted an association with agricultural use of lindane, but not with DDT. However another case-control study indicated that chemotherapy for non-Hodgkins Lymphoma affects blood levels of organochlorines, which could result in misclassification of exposure and distort findings. Farmers were found to be at elevated risk for prostate cancer in a study of mortality in 24 states.